title: Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.
abstract: To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.
authors.affiliation: Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Devlin
authors.forename: M J
authors.initials: MJ
authors.lastname: Brosnan
authors.forename: D
authors.initials: D
authors.lastname: Graham
authors.forename: J J
authors.initials: JJ
authors.lastname: Morton
authors.forename: A R
authors.initials: AR
authors.lastname: McPhaden
authors.forename: M
authors.initials: M
authors.lastname: McIntyre
authors.forename: C A
authors.initials: CA
authors.lastname: Hamilton
authors.forename: J L
authors.initials: JL
authors.lastname: Reid
authors.forename: A F
authors.initials: AF
authors.lastname: Dominiczak
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D002217:Carbachol / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology*; D002453:Cell Cycle; D004247:DNA / Q000032:analysis; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011123:Polyploidy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D012333:RNA, Messenger; D009599:Nitroprusside; D010656:Phenylephrine; D000450:Aldosterone; D002217:Carbachol; D004247:DNA; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester